rs334708

Variant names:

• chr1-61147924-G-A
• rs334708
• NM_001134673.4:c.559+59244G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-61147924-G-A
• chr1-61147924-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001134673.4(NFIA):​c.559+59244G>A variant causes a intron change. The variant allele was found at a frequency of 0.826 in 152,056 control chromosomes in the GnomAD database, including 53,007 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.83 (53007 hom., cov: 31)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.93
• Publications: 2 publications found

Genes affected

NFIA (HGNC:7784): (nuclear factor I A) This gene encodes a member of the NF1 (nuclear factor 1) family of transcription factors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

NFIA Gene-Disease associations (from GenCC):

• brain malformations with or without urinary tract defects

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• chromosome 1p32-p31 deletion syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIA	NM_001134673.4	c.559+59244G>A		intron_variant	Intron 2 of 10	ENST00000403491.8	NP_001128145.1
NFIA	NM_001145512.2	c.694+59244G>A		intron_variant	Intron 3 of 11		NP_001138984.1
NFIA	NM_001145511.2	c.535+59244G>A		intron_variant	Intron 2 of 10		NP_001138983.1
NFIA	NM_005595.5	c.559+59244G>A		intron_variant	Intron 2 of 9		NP_005586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIA	ENST00000403491.8	c.559+59244G>A		intron_variant	Intron 2 of 10	1	NM_001134673.4	ENSP00000384523.3

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125490 AN: 151938 Hom.: 52998 Cov.: 31

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.856

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.826 AC: 125532 AN: 152056 Hom.: 53007 Cov.: 31 AF XY: 0.826 AC XY: 61400 AN XY: 74336

African (AFR) AF: 0.663 AC: 27447 AN: 41410

American (AMR) AF: 0.835 AC: 12761 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3153 AN: 3472

East Asian (EAS) AF: 0.569 AC: 2932 AN: 5156

South Asian (SAS) AF: 0.799 AC: 3849 AN: 4818

European-Finnish (FIN) AF: 0.926 AC: 9817 AN: 10598

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62682 AN: 68002

Other (OTH) AF: 0.848 AC: 1793 AN: 2114

Alfa AF: 0.896 Hom.: 36133

Bravo AF: 0.811

Asia WGS AF: 0.611 AC: 2126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Benign	0.75
PhyloP100		3.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs334708; hg19: chr1-61613596;